title: CD44 is associated with proliferation, rather than a specific cancer stem cell population, in cultured canine cancer cells.
abstract: BACKGROUND
  The cancer stem cell hypothesis proposes that tumours are maintained by a population of cancer stem cells (CSC), which must be eradicated to prevent disease relapse after treatment. Cells expressing high levels of CD44 have been identified as candidate CSC in a variety of human tumours. This study sought to investigate CD44 expression and its potential as a CSC marker in canine cancer.
  
  
  METHODS
  CD44 expression in several canine cancer cell lines was determined by flow cytometry. Cells with low and high levels of CD44 expression were examined for differences in growth characteristics, colony forming ability, drug sensitivity and cell cycle profile.
  
  
  RESULTS
  CD44(High) cells demonstrated enhanced growth and colony forming capacity, under both adherent and low-density serum free ("tumoursphere") conditions. However, no difference in sensitivity to doxorubicin was seen between the two populations. Moreover, whilst most CD44(Low) cells were in resting or G₁ growth phase, an increased proportion of CD44(High) cells were in G₂M phase of the cell cycle. Upon proliferation in culture, both populations gave rise to progeny with a full spectrum of CD44 expression.
  
  
  CONCLUSIONS
  CD44 expression is associated with proliferation in cultured canine cancer cells, but transient and fluctuating expression may limit its utility as a CSC marker.
authors.affiliation: Comparative Oncology and Stem Cell Research Group, Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, Midlothian EH259RG, United Kingdom. t.m.blacking@sms.ed.ac.uk
authors.forename: T M
authors.initials: TM
authors.lastname: Blacking
authors.forename: M
authors.initials: M
authors.lastname: Waterfall
authors.forename: D J
authors.initials: DJ
authors.lastname: Argyle
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000502:physiology; D000954:Antigens, Surface / Q000276:immunology; D002453:Cell Cycle / Q000276:immunology / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004283:Dog Diseases / Q000276:immunology* / Q000503:physiopathology; D004285:Dogs; D005434:Flow Cytometry / Q000662:veterinary; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000502:physiology*; D009369:Neoplasms / Q000276:immunology* / Q000503:physiopathology; D014410:Tumor Stem Cell Assay / Q000662:veterinary
chemical_list: D000912:Antibodies, Neoplasm; D000954:Antigens, Surface; D018960:Hyaluronan Receptors